Thanks to the National 1Institutes of Health (EB-04285, MW) and (CA-115531 and RR-02584, ADS) and the Robert A. Welch Foundation (AT-584, ADS) for financial support of this work. X-ray diffraction was performed at the Robert A. Welch Foundation funded Texas Center for Crystallography at Rice University.
Macrocyclic compounds, Contrast media (Diagnostic imaging) -- Synthesis, Contrast-enhanced magnetic resonance imaging, Magnetic resonance imaging, Rare earth metals -- Magnetic properties
Interest in macrocyclic lanthanide complexes such as DOTA is driven largely through interest in their use as contrast agents for MRI. The lanthanide tetraamide derivatives of DOTA have shown considerable promise as PARACEST agents, taking advantage of the slow water exchange kinetics of this class of complex. We postulated that water exchange in these tetraamide complexes could be slowed even further by introducing a group to sterically encumber the space above the water coordination site, thereby hindering the departure and approach of water molecules to the complex. The ligand 8O2-bridged-DOTAM was synthesized in a 34% yield from cyclen. It was found that the lanthanide complexes of this ligand did not possess a water molecule in the inner coordination sphere of the bound lanthanide. The crystal structure of the ytterbium complex revealed that distortions to the coordination sphere were induced by the steric constraints imposed on the complex by the bridging unit. The extent of the distortion was found to increase with increasing ionic radius of the lanthanide ion, eventually resulting in a complete loss of symmetry in the complex. Because this ligand system is bicyclic, the conformation of each ring in the system is constrained by that of the other, in consequence inclusion of the bridging unit in the complexes means only a twisted square antiprismatic coordination geometry is observed for complexes of 8O2-bridged-DOTAM.
Vipond, J., Woods, M., Zhao, P., Tircsó, G., Ren, J., Bott, S. G., ... & Sherry, A. D. (2007). A bridge to coordination isomer selection in lanthanide (III) DOTA-tetraamide complexes. Inorganic chemistry, 46(7), 2584-2595.